The present invention is generally related to a multichannel particle counting method and a device for practicing the method. Such counters can be used to count micro-scale and/or nano-scale particles and the like. Counters within the scope of the present invention generally operate by sensing changes in resistance, conductivity, conductance or the like. More particularly, as a particle passes through a channel, it disrupts the ion current therein, thus increasing the channel's resistance.
Quantitative measurements of the size and concentration of micro and nano scale particles has been accomplished using Coulter counters. A typical Coulter counter device comprising a single micropore that separates two chambers containing electrolyte solutions. When a particle flows through the microchannel, it results in the electrical resistance change of the liquid filled microchannel. The resistance change can be recorded in terms of current or voltage pulses, which can be correlated to size, mobility, surface charge and concentration of the particles. Due to the simple construction of these devices and the reliable sensing method, Coulter devices have found application in a broad range of particle analyses from blood cells to polymeric beads, DNA, virus particles and even metal ions.
One substantial disadvantage of existing Coulter counters is their low throughput efficiency, which substantially extends measurement times. Coulter counting measurement relies on particles passing through a tiny orifice (microchannel) one by one from one chamber to the other. Thus, in order to complete sampling of a small number of particle solutions, thousands of micro or nanoparticles have to pass through the orifice one by one, which could be prohibitively time consuming. For instance, one estimate shows that a sample having a particle concentration of 108 particles/mL (v/v ratio 0.026%) requires 27.7 hours to complete a measurement, assuming each particle takes about 0.05 seconds to pass through the orifice, only one particle is resident in the orifice at any given time, and assuming a 0.01 mL sample volume. The measurement time is further extended as the orifice size decreases.
A variety of approaches to alleviating the time-measurement issue have been tried in the art. For instance, electroosmosis and electrophoresis have been applied to drive particles and electrolyte fluids. However, both methods have fallen short. Particularly, in order to obtain a sufficient fluid velocity, a strong external electric field must be applied leading to high power consumption, which is not practical for most biological applications. Furthermore, electroosmosis and electrophoresis only drive charged particles. Thus, if the particles are only slightly charged or neutral, electric forces are too weak to substantially shorten measurement time. Accordingly, there is a deficiency in the art in that it lacks a high throughput particle counting method and device, which is compatible with biological particles.
The present invention overcomes the challenges and deficiencies of the prior art by providing a particle counting method and device having a plurality of orifices, which are capable of counting particles in parallel with one another. Furthermore, such systems are compatible with biological particles inasmuch as it circumvents the need for electrophoretic or electroosmotic fields. Thus, the present invention fills a substantial gap in the art.